학술논문
Inhibition of the Cell Uptake of Delta and Omicron SARS-CoV-2 Pseudoviruses by N -Acetylcysteine Irrespective of the Oxidoreductive Environment.
Document Type
Academic Journal
Author
La Maestra S; Department of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, Italy.; Garibaldi S; Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, 16132 Genoa, Italy.; Balansky R; National Centre of Oncology, 1756 Sofia, Bulgaria.; D'Agostini F; Department of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, Italy.; Micale RT; Department of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, Italy.; De Flora S; Department of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, Italy.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
Subject
Language
English
Abstract
The binding of SARS-CoV-2 spikes to the cell receptor angiotensin-converting enzyme 2 (ACE2) is a crucial target both in the prevention and in the therapy of COVID-19. We explored the involvement of oxidoreductive mechanisms by investigating the effects of oxidants and antioxidants on virus uptake by ACE2-expressing cells of human origin (ACE2-HEK293). The cell uptake of pseudoviruses carrying the envelope of either Delta or Omicron variants of SARS-CoV-2 was evaluated by means of a cytofluorimetric approach. The thiol N -acetyl-L-cysteine (NAC) inhibited the uptake of both variants in a reproducible and dose-dependent fashion. Ascorbic acid showed modest effects. In contrast, neither hydrogen peroxide (H 2 O 2 ) nor a system-generating reactive oxygen species (ROS), which play an important role in the intracellular alterations produced by SARS-CoV-2, were able to affect the ability of either Delta or Omicron SARS-CoV-2 pseudoviruses to be internalized into ACE2-expressing cells. In addition, neither H 2 O 2 nor the ROS generating system interfered with the ability of NAC to inhibit that mechanism. Moreover, based on previous studies, a preventive pharmacological approach with NAC would have the advantage of decreasing the risk of developing COVID-19, irrespective of its variants, and at the same time other respiratory viral infections and associated comorbidities.